Phospholipase C Signalling

磷脂酶－C之訊息傳遞

Mark R. Smith ； Ya-Lun Liu ； Sue Goo Rhee ； 孔祥復(Hsiang-Fu Kung)

《Zoological Studies》 34卷3期 (1995/07) Pp. 141-148

摘要

脂類早先被認為只在能量儲存與細胞膜構造方面扮演重要角色，最近研究顯示，磷脂亦扮演在細胞活化與訊息傳遞之介體角色。磷脂酶是調控許多訊息傳遞路徑的關鍵酶，當細胞接受（生長）分化因子、激素、及神經傳遞物刺激時，肌醇磷脂特異性之磷脂酶－C（PLC）催化磷脂肌醇4，5-雙磷酸（PIP2）水解，產生肌酸三磷酸（IP3）與甘油二酯（DAG），此水解產物（IP3與DAG）為細胞內第二訊息傳遞者，可放大細胞初級訊息傳遞：IP3引發細胞之鈣離子流動，DAG可活化蛋白質激酶－C。本文主要描述PLC兩方面之研究結果：（一） PLC同工酶之特性研究、純化與分子選殖，（二） PLC同工酶酵素活性及催化細胞好裂之關連性。我們除了回顧PLC訊息傳遞已發表之研究成果外，也同時敘述一些尚未發表之新結果。將PLC-β或PLC-γ注射到生長後好裂靜止之NIH/3T3細胞裡面，可引發DNA合成及細胞增殖， 而PLC-δ則無此活性。PLC-y之單株抗體可阻斷血清引發之NIH/3T3細胞增殖與致癌因子（fes，src，ras與mas）轉形之NIH/3T3細胞生長，而Raf轉形之細胞則不受抗體注射所抑制。因此，血清與fes，src，ras與mos等致癌基因引發之纖維母細胞增殖，需要透過PLC-γ之訊息傳遞。

關鍵字

磷脂酶-C ； 訊息傳遞

並列摘要

Lipids were originally thought to play important roles only in energy storage and membrane structure. Recent experimental evidence indicate that phospholipids also play criticalroles as mediators in cell activation and signal transduction. Phospholipases are the key enzymes thatregulate various signalling pathways. Inositol phospholipid-specific phospholipase C (PLC) catalyzes thehydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), to generate inositol triphosphate (IP3) and dia-cylglycerol (DAG) in response to several receptor-binding growth/differentiation factors, hormones, andneurotransmitters. The hydrolysis products serve as intracellular second messenger molecules which amplifythe initial signalling events leading to cellular calcium mobilization by IP3 and protein kinase C (PKC) ac-tivation by DAG. In this article, we address two aspects to PLC signalling: 1. characterization, purificationand molecular cloning of PLC isozymes; and 2. mitogenic and catalytic activities of PLC isozymes. In addi-tion to reviewing published data on PLC signalling, we have included new data that examine the mitogenicactivity of the PLC isozymes. PLC-,B and PLC--y induce DNA synthesis after microinjection into quiescentNIH/3T3 cells, while PLC-IJ does not exhibit this activity. Monoclonal antibodies to PLC--y were shown toblock serum-stimulated growth of NIH/3T3 cells and several oncogenes transformed NIH/3T3 cells (fes, src, ras and mos), yet Raf transformed cells were not inhibited by antibody injection. Thus, PLC--y signalling is required for serum- and (fes, src, ras and mos) oncogene-induced proliferation of fibroblasts.

並列關鍵字

Phospholipase C ； signal transduction